Hyperglycemic crisis and electrolyte imbalances

Roscoe JM, Halperin ML, Rolleston FS, Goldstein MB. Hyperosmolar hyperglycemic nonketotic Workout apparel recommendations coma. Thereafter, venous electro,yte should yHperglycemic assessed every 2 h until the pH rises to 7. If they are, this means they would be appropriate for a step-down bed. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis.

Hyperglycemic crisis and electrolyte imbalances -
This could potentially be an area for further investigation on the transition process and its implication on patient outcomes 24 , Insulin sequestering to plastic IV tubing has been described, resulting in insulin wasting and dose inaccuracy 34 , Flushing the IV tube with a priming fluid of 20 mL is adequate to minimize the insulin losses to IV tube 34 , Patients with hyperglycemic crisiss are at a higher risk of developing hypokalemia due to multifactorial process 1 , Insulin therapy, correction of acidosis, and hydration all together lead to the development of hypokalemia 1 , Additionally, volume depletion seen with hyperglycemic crisis leads to secondary hyperaldosteronism, which exacerbates hypokalemia by enhancing urinary potassium excretion 1 , Serum potassium level should be obtained immediately upon presentation and prior to initiating insulin therapy 1 , Potassium replacement is required regardless of the baseline serum potassium level due to hydration and insulin therapy, except among renal failure patients 1 , It is suggested to administer 20 —30 mEq potassium in each liter of intravenous fluid to keep a serum potassium concentration within the normal range 1 , In addition to possible hypokalemia, patients with the hyperglycemic crisis could present with hypophosphatemia 1 , Osmotic diuresis during hyperglycemic crisis increases the urinary phosphate excretion, and insulin therapy enhances intracellular phosphate shift 1 , Phosphate replacement is not a fundamental part of hyperglycemic crisis management, given the lack of evidence of clinical benefit 1 , 29 , A special consideration with phosphate administration is the secondary hypocalcemia 1 , 29 , Acidemia associated with DKA results from the overproduction of ketoacids, generated from the haptic metabolism of free fatty acids.

This hepatic metabolism occurs as a result of insulin resistance and an increase in the counterregulatory hormones contributing to the pathophysiology of DKA 37 , Tissue acidosis could lead to impaired myocardial contractility, systemic vasodilatation, inhibition of glucose utilization by insulin, and lowering the levels of 2,3-diphosphoglycerate 2,3-DPG in erythrocytes 37 — Sodium bicarbonate decreases the hemoglobin-oxygen affinity leading to tissue hypoxia; moreover, it is associated with hypernatremia, hypocalcemia, hypokalemia, hypercapnia, prolonged QTc interval, intracellular acidosis, and metabolic alkalosis 39 , The use of adjuvant sodium bicarbonate in the setting of DKA consistently shows a lack of clinical benefit and should be prescribed on a case-by-case basis.

Although this recommendation was not supported by solid evidence; many clinicians adopt the practice to avoid the unwanted side effect of severe metabolic acidosis.

Sodium bicarbonate moves potassium intracellularly, however, clinical benefit is uncertain, and the use is controversial 41 , Prompt therapy for patients with hyperglycemic crisis is essential in reducing morbidity and mortality 6 , If not treated or treated ineffectively, the prognosis can include serious complications such as seizures, organ failures, coma, and death 6 , When treatment is delayed, the overall mortality rate of HHS is higher than that of DKA, especially in older patients.

This difference in prognoses was comparable when patients were matched for age In DKA, prolonged hypotension can lead to acute myocardial and bowel infarction 6 , The kidney plays a vital role in normalizing massive pH and electrolyte abnormalities 6 , Patients with prior kidney dysfunction or patients who developed end-stage chronic kidney disease worsen the prognosis considerably 6 , In HHS, severe dehydration may predispose the patient to complications such as myocardial infarction, stroke, pulmonary embolism, mesenteric vein thrombosis, and disseminated intravascular coagulation 6 , The VTE risk was higher than diabetic patients without hyperglycemic crisis or diabetic acidosis patients Management of hyperglycemic crisis may also be associated with significant complications include electrolyte abnormalities, hypoglycemia, and cerebral edema 7.

This is due to the use of insulin and fluid replacement therapy 4 , 5. Therefore, frequent electrolytes and blood glucose concentrations monitoring are essential while insulin infusions and fluid replacements are continued 4 , 5.

Cerebral edema is a rare but severe complication in children and adolescents and rarely affects adult patients older than 28 7. This could be due to the lack of cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents The exact mechanism of cerebral edema development is unknown.

Some reports suggest that the risk of cerebral edema during hyperglycemic crisis management might be induced by rapid hydration, especially in the pediatric population. However, a recent multicenter study for children with DKA who were randomized to receive isotonic versus hypotonic sodium IV fluid with different infusions rates did not show a difference in neurological outcomes Early identification and prompt therapy with mannitol or hypertonic saline can prevent neurological deterioration from DKA management 7 , Furthermore, higher blood urea nitrogen BUN and sodium concentrations have been identified as cerebral edema risk factors Thus, careful hydration with close electrolytes and BUN is recommended Other serious complications of hyperglycemic crisis may include transient AKI, pulmonary edema in patients with congestive heart failure, myocardial infarction, a rise in pancreatic enzymes with or without acute pancreatitis, cardiomyopathy, rhabdomyolysis in patients presented with severe dehydration 7 , All authors have contributed equally in writing, organizing, and reviewing this publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Management of Hyperglycemic Crises in Patients With Diabetes. Diabetes Care 24 1 — Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic Crises in Adult Patients With Diabetes: A Consensus Statement From the American Diabetes Association.

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Case of Ketoacidosis by a Sodium-Glucose Cotransporter 2 Inhibitor in a Diabetic Patient With a Low-Carbohydrate Diet. J Diabetes Investig , 6 5 — Umpierrez GE, Murphy MB, Kitabchi AE.

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome. Diabetes Spectr 15 1 Kraut JA, Madias NE. Serum Anion Gap: Its Uses and Limitations in Clinical Medicine. Clin J Am Soc Nephrol 2 1 — Dhatariya K, Savage M, Claydon A, et al. Joint British Diabetes Societies for Inpatient Care JBDS-IP Revised Guidelines.

The Management of Diabetic Ketoacidosis in Adults Revised Google Scholar. Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic Ketoacidosis and Hyperosmolar State. In: DeFronzo RA, Ferrannini E, Zimmet P, Alberti KGMM, editors. International Textbook of Diabetes Mellitus. Trachtenbarg DE.

Diabetic Ketoacidosis. Am Fam Phys 71 9 — Katz MA. Hyperglycemia-Induced Hyponatremia-Calculation of Expected Serum Sodium Depression. N Engl J Med 16 —4. Rudloff E, Hopper K. Crystalloid and Colloid Compositions and Their Impact. Front Vet Sci Semler MW, Kellum JA.

Balanced Crystalloid Solutions. Am J Respir Crit Care Med 8 — Van Zyl DG, Rheeder P, Delport E. QJM 4 — Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation With Balanced Electrolyte Solution Prevents Hyperchloremic Metabolic Acidosis in Patients With Diabetic Ketoacidosis. Am J Emerg Med 29 6 —4.

Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials.

JAMA Netw. Open 3 11 :e Ramanan M, Attokaran A, Murray L, Bhadange N, Stewart D, Rajendran G, et al. Sodium Chloride or Plasmalyte Evaluation in Severe Diabetic Ketoacidosis Scope-Dka - a Cluster, Crossover, Randomized, Controlled Trial.

Intensive Care Med 47 11 — Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JAE, Courtney CH, et al. Joint British Diabetes Societies Guideline for the Management of Diabetic Ketoacidosis: Diabetic Ketoacidosis Guidelines.

Diabetic Med 28 5 — Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, et al. Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis: A Randomized Controlled Trial.

Diabetes Care 32 7 —9. Laskey D, Vadlapatla R, Hart K. Stability of High-Dose Insulin in Normal Saline Bags for Treatment of Calcium Channel Blocker and Beta Blocker Overdose.

Clin Toxicol 54 9 — Lindsay R, Bolte RG. The Use of an Insulin Bolus in Low-Dose Insulin Infusion for Pediatric Diabetic Ketoacidosis. Pediatrs Emerg Care 5 2 —9. Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J.

Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis? Diabetes Care 31 11 Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al.

ISPAD Clinical Practice Consensus Guidelines Diabetic Ketoacidosis and the Hyperglycemic Hyperosmolar State. Pediatr Diabetes — Umpierrez GE, Latif K, Stoever J, Cuervo R, Park L, Freire AX, et al. Efficacy of Subcutaneous Insulin Lispro Versus Continuous Intravenous Regular Insulin for the Treatment of Patients With Diabetic Ketoacidosis.

Am J Med 5 —6. Ersöz HÖ, Ukinc K, Köse M, Erem C, Gunduz A, Hacihasanoglu AB, et al. Subcutaneous Lispro and Intravenous Regular Insulin Treatments are Equally Effective and Safe for the Treatment of Mild and Moderate Diabetic Ketoacidosis in Adult Patients: SC Lispro and IV Regular Insulin Treatments in DKA.

Int J Clin Pract 60 4 — Huang SK, Huang CY, Lin CH, Cheng BW, Chiang YT, Lee YC, et al. Acute Kidney Injury is a Common Complication in Children and Adolescents Hospitalized for Diabetic Ketoacidosis.

Shimosawa T, Ed. PloS One 15 10 :e Frankel AH, Kazempour-Ardebili S, Bedi R, Chowdhury TA, De P, El-Sherbini N, et al. Management of Adults With Diabetes on the Haemodialysis Unit: Summary of Guidance From the Joint British Diabetes Societies and the Renal Association.

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However, additional prospective studies are needed to document reduction of DKA incidence with the use of continuous subcutaneous insulin infusion devices Underlying medical illness that provokes the release of counterregulatory hormones or compromises the access to water is likely to result in severe dehydration and HHS.

In most patients with HHS, restricted water intake is due to the patient being bedridden and is exacerbated by the altered thirst response of the elderly. Elderly individuals with new-onset diabetes particularly residents of chronic care facilities or individuals with known diabetes who become hyperglycemic and are unaware of it or are unable to take fluids when necessary are at risk for HHS 10 , Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, and pentamidine, may precipitate the development of HHS or DKA 4.

Recently, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs may cause hyperglycemia and even DKA or HHS 26 , An increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes.

Observational and prospective studies indicate that over half of newly diagnosed adult African American and Hispanic subjects with unprovoked DKA have type 2 diabetes 28 , , , — The clinical presentation in such cases is acute as in classical type 1 diabetes ; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents.

In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of β-cell destruction, and the ability to discontinue insulin therapy during follow-up 28 , 31 , This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes.

At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA 28 , 31 , The process of HHS usually evolves over several days to weeks, whereas the evolution of the acute DKA episode in type 1 diabetes or even in type 2 diabetes tends to be much shorter.

Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present with DKA with no prior clues or symptoms. For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, weight loss, vomiting, dehydration, weakness, and mental status change.

Physical findings may include poor skin turgor, Kussmaul respirations in DKA , tachycardia, and hypotension. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS.

Focal neurologic signs hemianopia and hemiparesis and seizures focal or generalized may also be features of HHS 4 , Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation.

Severe hypothermia, if present, is a poor prognostic sign Caution needs to be taken with patients who complain of abdominal pain on presentation because the symptoms could be either a result of the DKA or an indication of a precipitating cause of DKA, particularly in younger patients or in the absence of severe metabolic acidosis 34 , Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.

The diagnostic criteria for DKA and HHS are shown in Table 1. The initial laboratory evaluation of patients include determination of plasma glucose, blood urea nitrogen, creatinine, electrolytes with calculated anion gap , osmolality, serum and urinary ketones, and urinalysis, as well as initial arterial blood gases and a complete blood count with a differential.

An electrocardiogram, chest X-ray, and urine, sputum, or blood cultures should also be obtained. The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis blood pH, bicarbonate, and ketones and the presence of altered mental status 4.

Significant overlap between DKA and HHS has been reported in more than one-third of patients Severe hyperglycemia and dehydration with altered mental status in the absence of significant acidosis characterize HHS, which clinically presents with less ketosis and greater hyperglycemia than DKA.

This may result from a plasma insulin concentration as determined by baseline and stimulated C-peptide [ Table 2 ] adequate to prevent excessive lipolysis and subsequent ketogenesis but not hyperglycemia 4.

The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration. Assessment of augmented ketonemia is usually performed by the nitroprusside reaction, which provides a semiquantitative estimation of acetoacetate and acetone levels.

Although the nitroprusside test both in urine and in serum is highly sensitive, it can underestimate the severity of ketoacidosis because this assay does not recognize the presence of β-hydroxybutyrate, the main metabolic product in ketoacidosis 4 , If available, measurement of serum β-hydroxybutyrate may be useful for diagnosis Accumulation of ketoacids results in an increased anion gap metabolic acidosis.

Hyperglycemia is a key diagnostic criterion of DKA; however, a wide range of plasma glucose can be present on admission.

Elegant studies on hepatic glucose production rates have reported rates ranging from normal or near normal 38 to elevated 12 , 15 , possibly contributing to the wide range of plasma glucose levels in DKA that are independent of the severity of ketoacidosis This could be due to a combination of factors, including exogenous insulin injection en route to the hospital, antecedent food restriction 39 , 40 , and inhibition of gluconeogenesis.

On admission, leukocytosis with cell counts in the 10,—15, mm 3 range is the rule in DKA and may not be indicative of an infectious process. In ketoacidosis, leukocytosis is attributed to stress and maybe correlated to elevated levels of cortisol and norepinephrine The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia.

An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss. To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1.

Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation 9 , Serum potassium concentration may be elevated because of an extracellular shift of potassium caused by insulin deficiency, hypertonicity, and acidemia Patients with low normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia.

Pseudonormoglycemia 44 and pseudohyponatremia 45 may occur in DKA in the presence of severe chylomicronemia.

The admission serum phosphate level in patients with DKA, like serum potassium, is usually elevated and does not reflect an actual body deficit that uniformly exists due to shifts of intracellular phosphate to the extracellular space 12 , 46 , Insulin deficiency, hypertonicity, and increased catabolism all contribute to the movement of phosphate out of cells.

A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis; however, lipase could also be elevated in DKA in the absence of pancreatitis Not all patients with ketoacidosis have DKA. DKA must also be distinguished from other causes of high—anion gap metabolic acidosis, including lactic acidosis; ingestion of drugs such as salicylate, methanol, ethylene glycol, and paraldehyde; and acute chronic renal failure 4.

Because lactic acidosis is more common in patients with diabetes than in nondiabetic persons and because elevated lactic acid levels may occur in severely volume-contracted patients, plasma lactate should be measured on admission.

A clinical history of previous drug abuse should be sought. Measurement of serum salicylate and blood methanol level may be helpful. Ethylene glycol antifreeze is suggested by the presence of calcium oxalate and hippurate crystals in the urine.

Paraldehyde ingestion is indicated by its characteristic strong odor on the breath. Because these intoxicants are low—molecular weight organic compounds, they can produce an osmolar gap in addition to the anion gap acidosis A recent report states that active cocaine use is an independent risk factor for recurrent DKA Recently, one case report has shown that a patient with diagnosed acromegaly may present with DKA as the primary manifestation of the disease In addition, an earlier report of pituitary gigantism was presented with two episodes of DKA with complete resolution of diabetes after pituitary apoplexy Successful treatment of DKA and HHS requires correction of dehydration, hyperglycemia, and electrolyte imbalances; identification of comorbid precipitating events; and above all, frequent patient monitoring.

Protocols for the management of patients with DKA and HHS are summarized in Fig. Protocol for management of adult patients with DKA or HHS.

Bwt, body weight; IV, intravenous; SC, subcutaneous. Initial fluid therapy is directed toward expansion of the intravascular, interstitial, and intracellular volume, all of which are reduced in hyperglycemic crises 53 and restoration of renal perfusion.

In the absence of cardiac compromise, isotonic saline 0. Subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urinary output. In general, 0. Fluid replacement should correct estimated deficits within the first 24 h.

In patients with renal or cardiac compromise, monitoring of serum osmolality and frequent assessment of cardiac, renal, and mental status must be performed during fluid resuscitation to avoid iatrogenic fluid overload 4 , 10 , 15 , Aggressive rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy During treatment of DKA, hyperglycemia is corrected faster than ketoacidosis.

The mainstay in the treatment of DKA involves the administration of regular insulin via continuous intravenous infusion or by frequent subcutaneous or intramuscular injections 4 , 56 , Randomized controlled studies in patients with DKA have shown that insulin therapy is effective regardless of the route of administration The administration of continuous intravenous infusion of regular insulin is the preferred route because of its short half-life and easy titration and the delayed onset of action and prolonged half-life of subcutaneous regular insulin 36 , 47 , Numerous prospective randomized studies have demonstrated that use of low-dose regular insulin by intravenous infusion is sufficient for successful recovery of patients with DKA.

Until recently, treatment algorithms recommended the administration of an initial intravenous dose of regular insulin 0. A recent prospective randomized study reported that a bolus dose of insulin is not necessary if patients receive an hourly insulin infusion of 0.

If plasma glucose does not decrease by 50—75 mg from the initial value in the first hour, the insulin infusion should be increased every hour until a steady glucose decline is achieved Fig.

Treatment with subcutaneous rapid-acting insulin analogs lispro and aspart has been shown to be an effective alternative to the use of intravenous regular insulin in the treatment of DKA. Treatment of patients with mild and moderate DKA with subcutaneous rapid-acting insulin analogs every 1 or 2 h in non—intensive care unit ICU settings has been shown to be as safe and effective as the treatment with intravenous regular insulin in the ICU 60 , The rate of decline of blood glucose concentration and the mean duration of treatment until correction of ketoacidosis were similar among patients treated with subcutaneous insulin analogs every 1 or 2 h or with intravenous regular insulin.

However, until these studies are confirmed outside the research arena, patients with severe DKA, hypotension, anasarca, or associated severe critical illness should be managed with intravenous regular insulin in the ICU.

Despite total-body potassium depletion, mild-to-moderate hyperkalemia is common in patients with hyperglycemic crises. Insulin therapy, correction of acidosis, and volume expansion decrease serum potassium concentration.

To prevent hypokalemia, potassium replacement is initiated after serum levels fall below the upper level of normal for the particular laboratory 5. Generally, 20—30 mEq potassium in each liter of infusion fluid is sufficient to maintain a serum potassium concentration within the normal range.

Rarely, DKA patients may present with significant hypokalemia. The use of bicarbonate in DKA is controversial 62 because most experts believe that during the treatment, as ketone bodies decrease there will be adequate bicarbonate except in severely acidotic patients.

Severe metabolic acidosis can lead to impaired myocardial contractility, cerebral vasodilatation and coma, and several gastrointestinal complications A prospective randomized study in 21 patients failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with an admission arterial pH between 6.

Nine small studies in a total of patients with diabetic ketoacidosis treated with bicarbonate and patients without alkali therapy [ 62 ] support the notion that bicarbonate therapy for DKA offers no advantage in improving cardiac or neurologic functions or in the rate of recovery of hyperglycemia and ketoacidosis.

Moreover, several deleterious effects of bicarbonate therapy have been reported, such as increased risk of hypokalemia, decreased tissue oxygen uptake 65 , cerebral edema 65 , and development of paradoxical central nervous system acidosis.

Despite whole-body phosphate deficits in DKA that average 1. Phosphate concentration decreases with insulin therapy. Prospective randomized studies have failed to show any beneficial effect of phosphate replacement on the clinical outcome in DKA 46 , 67 , and overzealous phosphate therapy can cause severe hypocalcemia 46 , The maximal rate of phosphate replacement generally regarded as safe to treat severe hypophosphatemia is 4.

No studies are available on the use of phosphate in the treatment of HHS. Patients with DKA and HHS should be treated with continuous intravenous insulin until the hyperglycemic crisis is resolved. Resolution of HHS is associated with normal osmolality and regain of normal mental status.

When this occurs, subcutaneous insulin therapy can be started. To prevent recurrence of hyperglycemia or ketoacidosis during the transition period to subcutaneous insulin, it is important to allow an overlap of 1—2 h between discontinuation of intravenous insulin and the administration of subcutaneous insulin.

Patients with known diabetes may be given insulin at the dosage they were receiving before the onset of DKA so long as it was controlling glucose properly. In insulin-naïve patients, a multidose insulin regimen should be started at a dose of 0.

Human insulin NPH and regular are usually given in two or three doses per day. More recently, basal-bolus regimens with basal glargine and detemir and rapid-acting insulin analogs lispro, aspart, or glulisine have been proposed as a more physiologic insulin regimen in patients with type 1 diabetes.

A prospective randomized trial compared treatment with a basal-bolus regimen, including glargine once daily and glulisine before meals, with a split-mixed regimen of NPH plus regular insulin twice daily following the resolution of DKA.

Hypoglycemia and hypokalemia are two common complications with overzealous treatment of DKA with insulin and bicarbonate, respectively, but these complications have occurred less often with the low-dose insulin therapy 4 , 56 , Frequent blood glucose monitoring every 1—2 h is mandatory to recognize hypoglycemia because many patients with DKA who develop hypoglycemia during treatment do not experience adrenergic manifestations of sweating, nervousness, fatigue, hunger, and tachycardia.

Hyperchloremic non—anion gap acidosis, which is seen during the recovery phase of DKA, is self-limited with few clinical consequences This may be caused by loss of ketoanions, which are metabolized to bicarbonate during the evolution of DKA and excess fluid infusion of chloride containing fluids during treatment 4.

Symptoms and signs of cerebral edema are variable and include onset of headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary changes, papilledema, bradycardia, elevation in blood pressure, and respiratory arrest Manitol infusion and mechanical ventilation are suggested for treatment of cerebral edema Many cases of DKA and HHS can be prevented by better access to medical care, proper patient education, and effective communication with a health care provider during an intercurrent illness.

Paramount in this effort is improved education regarding sick day management, which includes the following:. Emphasizing the importance of insulin during an illness and the reasons never to discontinue without contacting the health care team.

Similarly, adequate supervision and staff education in long-term facilities may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition.

The use of home glucose-ketone meters may allow early recognition of impending ketoacidosis, which may help to guide insulin therapy at home and, possibly, may prevent hospitalization for DKA.

In addition, home blood ketone monitoring, which measures β-hydroxybutyrate levels on a fingerstick blood specimen, is now commercially available The observation that stopping insulin for economic reasons is a common precipitant of DKA 74 , 75 underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious.

The rate of insulin discontinuation and a history of poor compliance accounts for more than half of DKA admissions in inner-city and minority populations 9 , 74 , Several cultural and socioeconomic barriers, such as low literacy rate, limited financial resources, and limited access to health care, in medically indigent patients may explain the lack of compliance and why DKA continues to occur in such high rates in inner-city patients.

These findings suggest that the current mode of providing patient education and health care has significant limitations. Addressing health problems in the African American and other minority communities requires explicit recognition of the fact that these populations are probably quite diverse in their behavioral responses to diabetes Significant resources are spent on the cost of hospitalization.

Based on an annual average of , hospitalizations for DKA in the U. A recent study 2 reported that the cost burden resulting from avoidable hospitalizations due to short-term uncontrolled diabetes including DKA is substantial 2.

However, the long-term impact of uncontrolled diabetes and its economic burden could be more significant because it can contribute to various complications. Because most cases occur in patients with known diabetes and with previous DKA, resources need to be redirected toward prevention by funding better access to care and educational programs tailored to individual needs, including ethnic and personal health care beliefs.

In addition, resources should be directed toward the education of primary care providers and school personnel so that they can identify signs and symptoms of uncontrolled diabetes and so that new-onset diabetes can be diagnosed at an earlier time. Recent studies suggest that any type of education for nutrition has resulted in reduced hospitalization In fact, the guidelines for diabetes self-management education were developed by a recent task force to identify ten detailed standards for diabetes self-management education An American Diabetes Association consensus statement represents the authors' collective analysis, evaluation, and opinion at the time of publication and does not represent official association opinion.

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Which diabetes medications Hyperglycemix should continue and which ones Body composition and endurance training should kmbalances stop. Workout apparel recommendations Hyperglycmic Although the diagnosis and treatment of leectrolyte ketoacidosis DKA in adults crieis in children share general principles, there are significant differences in Workout apparel recommendations application, largely related to the increased risk of life-threatening cerebral edema with DKA in children and adolescents. The specific issues related to treatment of DKA in children and adolescents are addressed in the Type 1 Diabetes in Children and Adolescents chapter, p. Diabetic ketoacidosis DKA and hyperosmolar hyperglycemic state HHS are diabetes emergencies with overlapping features. With insulin deficiency, hyperglycemia causes urinary losses of water and electrolytes sodium, potassium, chloride and the resultant extracellular fluid volume ECFV depletion.

American Diabetes Brown rice for breakfast Hyperglycemic Crises in Diabetes.

Ketoacidosis and hyperosmolar Hypeerglycemic are Low GI comfort foods two most imbalancew acute metabolic complications Building a healthy relationship with food for young athletes diabetes, even if managed imbalnaces.

These disorders Hyerglycemic occur in both type 1 and type 2 diabetes. The prognosis of both conditions is substantially Workout apparel recommendations Diabetic ketoacidosis the extremes of age and in the presence of imbalaances and hypotension 1 — Electroyte position statement Hypsrglycemic outline precipitating Mindful eating habits and recommendations Hyperglycmeic the diagnosis, treatment, and prevention electroolyte DKA and HHS.

It Hyperglyemic based on a previous technical review 11Insulin sensitivity and weight gain should be consulted for further information. Although the pathogenesis of DKA is better understood than imnalances of HHS, the basic Hypeeglycemic mechanism Hypegglycemic both disorders is a reduction in Hyperglcyemic net effective action of circulating insulin coupled with a Flaxseed for diabetes elevation of counterregulatory hormones, such as glucagon, mibalances, cortisol, and growth hormone.

These hormonal alterations in DKA aand HHS lead to increased hepatic and renal glucose production Food log and calorie counter impaired glucose utilization in imbzlances tissues, which result electtrolyte hyperglycemia and parallel changes in osmolality of the Hyperglyfemic space 12electrolye The combination of electrolytw deficiency and increased counterregulatory eectrolyte in DKA also leads to the release imbalahces free fatty Hyperglycemic crisis and electrolyte imbalances into the circulation from adipose tissue lipolysis and to unrestrained hepatic Hhperglycemic acid oxidation to ketone bodies β-hydroxybutyrate [β-OHB] and acetoacetatewith resulting ketonemia and metabolic acidosis.

On the electroljte hand, HHS may be caused by plasma imbalqnces concentrations that are inadequate to facilitate glucose utilization by anc tissues but adequate Insulin sensitivity and weight gain determined by residual C-peptide to prevent lipolysis and subsequent ketogenesis, although the Polyphenols and immune function for this is weak Both DKA Insulin sensitivity and weight gain HHS are mibalances with glycosuria, leading to osmotic diuresis, Insulin sensitivity and weight gain, with loss of water, electrolytd, potassium, and other electrolytes elwctrolyte15 — The laboratory and clinical characteristics of Crrisis and Hyperglhcemic are summarized in Tables 1 and 2.

As can be seen, DKA Hypegrlycemic HHS differ in magnitude of dehydration and degree of ketosis and acidosis. The most common precipitating factor in the development imbalancez DKA or Elfctrolyte is infection. Other precipitating electrolytte include cerebrovascular accident, alcohol abuse, pancreatitis, myocardial infarction, trauma, and drugs.

In addition, imbalancez type 1 diabetes or discontinuation of Plant-based athlete training fuel inadequate insulin in established type 1 inbalances commonly leads to the development of DKA. Elderly individuals with new-onset imbalsnces particularly residents of chronic care facilities or individuals with known diabetes who become hyperglycemic and are unaware of it or are unable to take fluids when necessary are at risk for HHS 6.

Drugs that affect carbohydrate metabolism, Hyperglyccemic Workout apparel recommendations corticosteroids, thiazides, and sympathomimetic agents Hyperflycemic. Factors that may lead to insulin omission in younger patients electrooyte fear of weight gain with improved metabolic control, fear of hypoglycemia, rebellion from authority, Hyperglyecmic stress of chronic disease The process of HHS usually evolves over several days to weeks, whereas imbalanes evolution of the acute DKA episode in type 1 diabetes or even in type imgalances diabetes tends to be much shorter.

Sports nutrition guidelines, the Diabetic foot care education symptomatic presentation may evolve or develop more acutely, and the patient may present in DKA with no prior Hhperglycemic or symptoms.

For both DKA and HHS, the Hyperglycemjc clinical Workout apparel recommendations includes a Workout apparel recommendations of polyuria, polydipsia, ad, weight loss, vomiting, abdominal pain only in DKAdehydration, weakness, clouding of sensoria, and Enhanced fat-burning rate coma.

Physical findings may include poor skin turgor, Kussmaul respirations in DKAelechrolyte, hypotension, alteration in mental status, ctisis, and ultimately coma more Natural Collagen Benefits in HHS.

Endoscopy has related this Weight and body shape to the presence of hemorrhagic gastritis.

Mental status can Ketoacidosis versus hypoglycemia symptoms from full alertness to Hypfrglycemic lethargy electrolyye coma, imbalanecs the latter more frequent in HHS.

Anx infection is a Hyperflycemic precipitating Hyperglycemic crisis and electrolyte imbalances imbalanced both DKA and Imbalancees, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation.

Hypothermia, if present, electrolytd a poor prognostic sign Caution needs Hyperglycemid be taken with patients who complain of abdominal pain on presentation, because the symptoms could be either a result or an indication of a precipitating cause particularly in younger patients of DKA.

Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis. Bacterial cultures of urine, blood, and throat, etc.

HbA 1c may be useful in determining whether this acute episode is the culmination of an evolutionary process in previously undiagnosed or poorly controlled diabetes or a truly acute episode in an otherwise well-controlled patient. A chest X-ray should also be obtained if indicated. Tables 1 and 2 depict typical laboratory findings in patients with DKA or HHS.

The majority of patients with hyperglycemic emergencies present with leukocytosis proportional to blood ketone body concentration. Serum sodium concentration is usually decreased because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia, and less commonly, serum sodium concentration may be falsely lowered by severe hypertriglyceridemia.

Serum potassium concentration may be elevated because of an extracellular shift of potassium caused by insulin deficiency, hypertonicity, and acidemia. Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia.

Amylase levels are elevated in the majority of patients with DKA, but this may be due to nonpancreatic sources, such as the parotid gland. A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis.

However, lipase could also be elevated in DKA. Abdominal pain and elevation of serum amylase and liver enzymes are noted more commonly in DKA than in HHS. Not all patients with ketoacidosis have DKA.

DKA must also be distinguished from other causes of high-anion gap metabolic acidosis, including lactic acidosis, ingestion of drugs such as salicylate, methanol, ethylene glycol, and paraldehyde, and chronic renal failure which is more typically hyperchloremic acidosis rather than high-anion gap acidosis.

Clinical history of previous drug intoxications or metformin use should be sought. Measurement of blood lactate, serum salicylate, and blood methanol level can be helpful in these situations.

Ethylene glycol antifreeze is suggested by the presence of calcium oxalate and hippurate crystals in the urine. Paraldehyde ingestion is indicated by its characteristic strong odor on the breath. Because these intoxicants are low-molecular weight organic compounds, they can produce an osmolar gap in addition to the anion gap acidosis 14 — Successful treatment of DKA and HHS requires correction of dehydration, hyperglycemia, and electrolyte imbalances; identification of comorbid precipitating events; and above all, frequent patient monitoring.

Guidelines for the management of patients with DKA and HHS follow and are summarized in Figs. Table 3 includes a summary of major recommendations and evidence gradings. Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion.

In the absence of cardiac compromise, isotonic saline 0. Subsequent choice for fluid replacement depends on the state of hydration, serum electrolyte levels, and urinary output.

In general, 0. Fluid replacement should correct estimated deficits within the first 24 h. In patients with renal or cardiac compromise, monitoring of serum osmolality and frequent assessment of cardiac, renal, and mental status must be performed during fluid resuscitation to avoid iatrogenic fluid overload 14 — 20 Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal profusion.

The need for vascular volume expansion must be offset by the risk of cerebral edema associated with rapid fluid administration. The 1st hour of fluids should be isotonic saline 0. Continued fluid therapy is calculated to replace the fluid deficit evenly over 48 h.

Therapy should include monitoring mental status to rapidly identify changes that might indicate iatrogenic fluid overload, which can lead to symptomatic cerebral edema 23 — Unless the episode of DKA is mild Table 1regular insulin by continuous intravenous infusion is the treatment of choice.

An initial insulin bolus is not recommended in pediatric patients; a continuous insulin infusion of regular insulin at a dose of 0.

Thereafter, the rate of insulin administration or the concentration of dextrose may need to be adjusted to maintain the above glucose values until acidosis in DKA or mental obtundation and hyperosmolarity in HHS are resolved. Ketonemia typically takes longer to clear than hyperglycemia. Direct measurement of β-OHB in the blood is the preferred method for monitoring DKA.

The nitroprusside method only measures acetoacetic acid and acetone. However, β-OHB, the strongest and most prevalent acid in DKA, is not measured by the nitroprusside method. During therapy, β-OHB is converted to acetoacetic acid, which may lead the clinician to believe that ketosis has worsened.

Therefore, assessments of urinary or serum ketone levels by the nitroprusside method should not be used as an indicator of response to therapy. During therapy for DKA or HHS, blood should be drawn every 2—4 h for determination of serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH for DKA.

Generally, repeat arterial blood gases are unnecessary; venous pH which is usually 0. With mild DKA, regular insulin given either subcutaneously or intramuscularly every hour is as effective as intravenous administration in lowering blood glucose and ketone bodies Thereafter, 0.

Once DKA is resolved, if the patient is NPO, continue intravenous insulin and fluid replacement and supplement with subcutaneous regular insulin as needed every 4 h. When the patient is able to eat, a multiple-dose schedule should be started that uses a combination of short- or rapid-acting and intermediate- or long-acting insulin as needed to control plasma glucose.

Continue intravenous insulin infusion for 1—2 h after the split-mixed regimen is begun to ensure adequate plasma insulin levels. An abrupt discontinuation of intravenous insulin coupled with a delayed onset of a subcutaneous insulin regimen may lead to worsened control; therefore, some overlap should occur in intravenous insulin therapy and initiation of the subcutaneous insulin regimen.

Patients with known diabetes may be given insulin at the dose they were receiving before the onset of DKA or HHS and further adjusted as needed for control.

Finally, some type 2 diabetes patients may be discharged on oral antihyperglycemic agents and dietary therapy. Despite total-body potassium depletion, mild to moderate hyperkalemia is not uncommon in patients with hyperglycemic crises.

Insulin therapy, correction of acidosis, and volume expansion decrease serum potassium concentration. To prevent hypokalemia, potassium replacement is initiated after serum levels fall below 5. Rarely, DKA patients may present with significant hypokalemia.

Bicarbonate use in DKA remains controversial Prospective randomized studies have failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with pH between 6. In patients with a pH of 6. Insulin, as well as bicarbonate therapy, lowers serum potassium; therefore, potassium supplementation should be maintained in intravenous fluid as described above and carefully monitored.

See Fig. Thereafter, venous pH should be assessed every 2 h until the pH rises to 7. See Kitabchi et al. Phosphate concentration decreases with insulin therapy.

Prospective randomized studies have failed to show any beneficial effect of phosphate replacement on the clinical outcome in DKA 32and overzealous phosphate therapy can cause severe hypocalcemia with no evidence of tetany 17 No studies are available on the use of phosphate in the treatment of HHS.

Continuous monitoring using a flowsheet Fig. Commonly, patients recovering from DKA develop hyperchloremia caused by the use of excessive saline for fluid and electrolyte replacement and transient non-anion gap metabolic acidosis as chloride from intravenous fluids replaces ketoanions lost as sodium and potassium salts during osmotic diuresis.

These biochemical abnormalities are transient and are not clinically significant except in cases of acute renal failure or extreme oliguria. Cerebral edema is a rare but frequently fatal complication of DKA, occurring in 0.
: Hyperglycemic crisis and electrolyte imbalances

JavaScript is disabled	Sodium bicarbonate moves potassium intracellularly, however, clinical benefit is uncertain, and the use is controversial 41 , Prompt therapy for patients with hyperglycemic crisis is essential in reducing morbidity and mortality 6 , If not treated or treated ineffectively, the prognosis can include serious complications such as seizures, organ failures, coma, and death 6 , When treatment is delayed, the overall mortality rate of HHS is higher than that of DKA, especially in older patients. This difference in prognoses was comparable when patients were matched for age In DKA, prolonged hypotension can lead to acute myocardial and bowel infarction 6 , The kidney plays a vital role in normalizing massive pH and electrolyte abnormalities 6 , Patients with prior kidney dysfunction or patients who developed end-stage chronic kidney disease worsen the prognosis considerably 6 , In HHS, severe dehydration may predispose the patient to complications such as myocardial infarction, stroke, pulmonary embolism, mesenteric vein thrombosis, and disseminated intravascular coagulation 6 , The VTE risk was higher than diabetic patients without hyperglycemic crisis or diabetic acidosis patients Management of hyperglycemic crisis may also be associated with significant complications include electrolyte abnormalities, hypoglycemia, and cerebral edema 7. This is due to the use of insulin and fluid replacement therapy 4 , 5. Therefore, frequent electrolytes and blood glucose concentrations monitoring are essential while insulin infusions and fluid replacements are continued 4 , 5. Cerebral edema is a rare but severe complication in children and adolescents and rarely affects adult patients older than 28 7. This could be due to the lack of cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents The exact mechanism of cerebral edema development is unknown. Some reports suggest that the risk of cerebral edema during hyperglycemic crisis management might be induced by rapid hydration, especially in the pediatric population. However, a recent multicenter study for children with DKA who were randomized to receive isotonic versus hypotonic sodium IV fluid with different infusions rates did not show a difference in neurological outcomes Early identification and prompt therapy with mannitol or hypertonic saline can prevent neurological deterioration from DKA management 7 , Furthermore, higher blood urea nitrogen BUN and sodium concentrations have been identified as cerebral edema risk factors Thus, careful hydration with close electrolytes and BUN is recommended Other serious complications of hyperglycemic crisis may include transient AKI, pulmonary edema in patients with congestive heart failure, myocardial infarction, a rise in pancreatic enzymes with or without acute pancreatitis, cardiomyopathy, rhabdomyolysis in patients presented with severe dehydration 7 , All authors have contributed equally in writing, organizing, and reviewing this publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care 32 7 — doi: PubMed Abstract CrossRef Full Text Google Scholar. Goyal A, Mathew UE, Golla KK, Mannar V, Kubihal S, Gupta Y, et al. A Practical Guidance on the Use of Intravenous Insulin Infusion for Management of Inpatient Hyperglycemia. Diabetes Metab Syndrome: Clin Res Rev 15 5 CrossRef Full Text Google Scholar. Saeedi P. 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Nonketotic hyperosmolar diabetic come in Down's syndrome. Jacobson R, Horenstein M, Kassel L. Hyperglycemia and hyperosmolarity in a brittle diabetic with thyrotoxicosis. Vinik A, Seftel H, Joffe BI. Metabolic findings in hyperosmolar non-ketotic diabetic stupor. Balsam MJ, Baker L, Kaye R. Hyperosmolar nonketotic come associated with diazoxide therapy for hypoglycemia. Dagnone LE, Reid JD, Green RN. Non-ketotic hyperosmolar coma with insulin resistance in a year-old girl. Evans CC, Littler WA, Meade JB. Hyperosmolar hyperglycemic non-ketotic diabetic coma complicating open heart surgery. Br Heart J. Doromal NM, Canter JW. Hyperosmolar hyperglycemic nonketotic coma complicating intravenous hyperalimentation. Surg Gynecol Obstet. Heggarty H, Trindade P, Bryan EM. Hyperglycaemia in hyperosmolar dehydration. Hobin FP, Maraist FB. Diabetic hyperosmolar nonketoacidotic coma complicated by mesenteric thrombosis. Case report. J Florida Med Assoc. Fernandez F, Hughes ER. Letter: non-ketotic hyperosmolar diabetic coma in an infant. Lampe EW II, Ruiz JO, Simmons RL, Najarian JS. Hyperglycemic non-ketotic coma after renal transplantation. Am J Surg. Tchertkoff V, Nayak SV, Kamath C, Salomon MI. Hyperosmolar nonketotic diabetic coma: vascular complications. J Am Geriatr Soc. Dorchy H, Pardou A, Weemaes I, Loeb H. Coma hyperosmolaire acido-cétosique sans cétonurie initiale: evolution favorable Acido-ketotic hyperosmolar coma without initial ketonuria: favorable course. Khaleeli AA, Wyman AL. Hyperosmolar non-ketotic diabetic coma induced by furosemide in modest dosage. Postgrad Med J. Goldman SL. Hyperglycemic hyperosmolar coma in a 9-month-old child. Joosten R, Frank M, Hörnchen H, Bertrams J. Hyperosmolar nonketotic diabetic coma. Eur J Pediatr. Yamashiro Y, Yamamoto T, Mayama H. Nonketotic hyperosmolar coma in two diabetic children. Acta Paediatr Scand. Asplund K, Eriksson S, Hägg E, Lithner F, Strand T, Wester PO. Hyperosmolar non-ketotic coma in diabetic stroke patients. Acta Med Scand. Altomonte L, Ghirlanda G, Palumbo P, Mann A, Greco V. Coma diabetico iperosmolare. Contributo casistico e revione della litteratura Hyperosmolar diabetic coma. Case reports and review of the literature. Minerva Med. Fujikawa LS, Meister DM, Nozik RA. Hyperosmolar hyperglycemic nonketotic coma. A complication of short-term systemic corticosteroid use. Hoffman WH, Fernados SS. Hyperglycemic hyperosmolar non-ketotic coma in a non-diabetic child. Khardori T, Soller NG. Hyperosmolar hyperglycemic nonketotic syndrome. Flynn JT, Bachynski BN, Rodrigues MM, Curless RG, Joshi B. Hyperglycemic acidotic comma in Kearns-Sayre syndrome. Trans Am Ophthalmol Soc. Schlepphorst E, Levin ME. Rhabdomyolysis associated with hyperosmolar nonketotic coma. Vernon DD, Postellon DC. Nonketotic hyperosmolal diabetic coma in a child: management with low-dose insulin infusion and intracranial pressure monitoring. Wachtel TJ, Silliman RA, Lamberton P. Prognostic factors in the diabetic hyperosmolar state. J Amer Geriatr Soc. McComb RD, Pfeiffer RF, Casey JH, Wolcott G, Till DJ. Lateral pontine and extrapontine myelinolysis associated with hypernatremia and hyperglycemia. Clin Neuropathol. Lustman CC, Guérin JM, Barbotin-Larrieu FE. Hyperosmolar nonketotic syndrome associated with rhabdomyolysis and acute kidney failure. Leung CB, Li PKT, Lui SF, Lai KN. Acute renal failure ARF caused by rhabdomyolysis due to diabetic hyperosmolar nonketotic coma: a case report and literature review. Renal Failure. Eidlitz-Markus T, Nussinovitch M, Varsano I, Kauschansky A. Nonketotic hyperosmolar coma in children. Isr J Med Sci. Piniés JA, Cairo G, Gaztambide S, Vazquez JA. Course and prognosis of patients with diabetic nonketotic hyperosmolar state. Diabete Metab. Yang JY, Cui XL, He XJ. Non-ketotic hyperosmolar coma complicating steroid treatment in childhood nephrosis. Pediatr Nephrol. Rother KI, Schwenk F II. An unusual case of nonketotic hyperglycemic syndrome during childhood. Mayo Clin Proc. Gottschalk ME, Ros SP, Zeller WP. The emergency management of hyperglycemic-hyperosmolar nonketotic coma in the pediatric patient. Tanaka S, Kobayashi T, Kawanami D, Hori A, Okubo N, Nakanishi K, et al. Paradoxical glucose infusion for hypernatraemia in diabetic hyperglycemic hyperosmolar syndrome. Milionis HJ, Liamis GL, Elisaf MS. Hyperosmolar syndrome in a patient with uncontrolled diabetes mellitus. Am J Kidney Dis. Pettigrew DC. Index of suspicion. Case 2. Diagnosis: hyperglycemic nonketotic hypertonicity HNKH. Pediatr Rev. Ka T, Takahashi S, Tsutsumi Z, Moriwaki Y, Yamamoto T, Fukuchi M. Hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure: a case report and review of the literature. Diabetes Nutr Metab. Ahlsson F, Gedeborg R, Hesselager G, Tuvemo T, Enblad P. Treatment of extreme hyperglycemia monitored with intracerebral microdialysis. Morales AE, Rosenbloom AL. Continuous monitoring using a flowsheet Fig. Commonly, patients recovering from DKA develop hyperchloremia caused by the use of excessive saline for fluid and electrolyte replacement and transient non-anion gap metabolic acidosis as chloride from intravenous fluids replaces ketoanions lost as sodium and potassium salts during osmotic diuresis. These biochemical abnormalities are transient and are not clinically significant except in cases of acute renal failure or extreme oliguria. Cerebral edema is a rare but frequently fatal complication of DKA, occurring in 0. It is most common in children with newly diagnosed diabetes, but it has been reported in children with known diabetes and in young people in their twenties 25 , Fatal cases of cerebral edema have also been reported with HHS. Clinically, cerebral edema is characterized by a deterioration in the level of consciousness, with lethargy, decrease in arousal, and headache. Neurological deterioration may be rapid, with seizures, incontinence, pupillary changes, bradycardia, and respiratory arrest. These symptoms progress as brain stem herniation occurs. The progression may be so rapid that papilledema is not found. Although the mechanism of cerebral edema is not known, it likely results from osmotically driven movement of water into the central nervous system when plasma osmolality declines too rapidly with the treatment of DKA or HHS. There is a lack of information on the morbidity associated with cerebral edema in adult patients; therefore, any recommendations for adult patients are clinical judgements, rather than scientific evidence. Hypoxemia and, rarely, noncardiogenic pulmonary edema may complicate the treatment of DKA. Hypoxemia is attributed to a reduction in colloid osmotic pressure that results in increased lung water content and decreased lung compliance. Patients with DKA who have a widened alveolo-arteriolar oxygen gradient noted on initial blood gas measurement or with pulmonary rales on physical examination appear to be at higher risk for the development of pulmonary edema. Many cases of DKA and HHS can be prevented by better access to medical care, proper education, and effective communication with a health care provider during an intercurrent illness. The observation that stopping insulin for economic reasons is a common precipitant of DKA in urban African-Americans 35 , 36 is disturbing and underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious. Sick-day management should be reviewed periodically with all patients. It should include specific information on 1 when to contact the health care provider, 2 blood glucose goals and the use of supplemental short-acting insulin during illness, 3 means to suppress fever and treat infection, and 4 initiation of an easily digestible liquid diet containing carbohydrates and salt. Most importantly, the patient should be advised to never discontinue insulin and to seek professional advice early in the course of the illness. Adequate supervision and help from staff or family may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition. Better education of care givers as well as patients regarding signs and symptoms of new-onset diabetes; conditions, procedures, and medications that worsen diabetes control; and the use of glucose monitoring could potentially decrease the incidence and severity of HHS. The annual incidence rate for DKA from population-based studies ranges from 4. Significant resources are spent on the cost of hospitalization. Many of these hospitalizations could be avoided by devoting adequate resources to apply the measures described above. Because repeated admissions for DKA are estimated to drain approximately one of every two health care dollars spent on adult patients with type 1 diabetes, resources need to be redirected toward prevention by funding better access to care and educational programs tailored to individual needs, including ethnic and personal health care beliefs. In addition, resources should be directed toward the education of primary care providers and school personnel so that they can identify signs and symptoms of uncontrolled diabetes and new-onset diabetes can be diagnosed at an earlier time. This has been shown to decrease the incidence of DKA at the onset of diabetes 30 , Protocol for the management of adult patients with DKA. Normal ranges vary by lab; check local lab normal ranges for all electrolytes. Obtain chest X-ray and cultures as needed. IM, intramuscular; IV, intravenous; SC subcutaneous. Protocol for the management of adult patients with HHS. This protocol is for patients admitted with mental status change or severe dehydration who require admission to an intensive care unit. For less severe cases, see text for management guidelines. IV, intravenous; SC subcutaneous. From Kitabchi et al. See text for details. Data are from Ennis et al. The highest ranking A is assigned when there is supportive evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered, including evidence from a meta-analysis that incorporated quality ratings in the analysis. An intermediate ranking B is given to supportive evidence from well-conducted cohort studies, registries, or case-control studies. A lower rank C is assigned to evidence from uncontrolled or poorly controlled studies or when there is conflicting evidence with the weight of the evidence supporting the recommendation. Expert consensus E is indicated, as appropriate. For a more detailed description of this grading system, refer to Diabetes Care 24 Suppl. The recommendations in this paper are based on the evidence reviewed in the following publication: Management of hyperglycemic crises in patients with diabetes Technical Review. Diabetes Care —, The initial draft of this position statement was prepared by Abbas E. Kitabchi, PhD, MD; Guillermo E. Umpierrez, MD; Mary Beth Murphy, RN, MS, CDE, MBA; Eugene J. Barrett, MD, PhD; Robert A. Kreisberg, MD; John I. Malone, MD; and Barry M. Wall, MD. The paper was peer-reviewed, modified, and approved by the Professional Practice Committee and the Executive Committee, October Revised Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Previous Article. Article Navigation. Position Statements January 01 Hyperglycemic Crises in Diabetes American Diabetes Association American Diabetes Association. This Site. Google Scholar. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1—. View large Download slide. Figure 2—. Figure 3—. Figure 4—. Table 1— Diagnostic criteria for DKA and HHS. View Large. Table 3— Summary of major recommendations. Therefore, to avoid the occurrence of cerebral edema, follow the recommendations in the position statement regarding a gradual correction of glucose and osmolality as well as the judicious use of isotonic or hypotonic saline, depending on serum sodium and the hemodynamic status of the patient. McGarry JD, Woeltje KF, Kuwajima M, Foster DW: Regulation of ketogenesis and the renaissance of carnitine palmitoyl transferase. Diabetes Metab Rev. DeFronzo RA, Matsuda M, Barrett E: Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy.
PATHOGENESIS	Factors associated with brain herniation in the treatment of diabetic ketoacidosis. Challenges in management of diabetic ketoacidosis in hemodialysis patients, case presentation and review of literature. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. J Postgrad Med Inst ;—3. Rashid MO, Sheikh A, Salam A, Farooq S, Kiran Z, Islam N.
Updates in the Management of Hyperglycemic Crisis	Hyponatremia: evaluating the correction factor for hyperglycemia. Goldman SL. Diabetes Canada Clinical Practice Guidelines Expert Committee, Goguen J, Gilbert J. Diabetes Technol Ther ;—3. Hyperosmolar hyperglycemic nonketotic coma complicating intravenous hyperalimentation. Am J Kidney Dis.
Diabetic ketoacidosis (DKA)	In hyperglycemia, glucose accumulation in the extracellular compartment contributes to tonicity Ton , which is expressed by the formula 9 :. Formula 1 provides accurate information on tonicity in hyperglycemia, except when high levels of plasma solids lower plasma water content e. However, this formula should not be used to guide the composition of the replacement solution. Hypertonicity in hyperglycemia results from gain of extracellular solute glucose and osmotic diuresis 2 , 5. Correction of hyperglycemia results in extracellular solute loss 11 and decrease in tonicity The tonicity of the replacement solutions should correct the component of hypertonicity resulting from osmotic diuresis 2 , 5. The tonicity of replacement solutions should be based on the projected value of [Na] after normalization of [Glu] 2 , 6 , 8. The corrected [Na] is calculated using a predicted value of the change in [Na] Δ[Na] that results directly from the required change in [Glu] Δ[Glu] and is applied in the evaluation of the component of hyperglycemic hypertonicity that results from osmotic diuresis. The value of the coefficient used to calculate the corrected [Na] is a point of dispute This perspective article reviews the sources of various estimates of the coefficient for the corrected [Na] and clinical studies providing evidence for the appropriate coefficient. Then, it computes the corrected [Na] in reports of various categories of hyperglycemic crises, and based on these last reports, provides a frame for the clinical application of the corrected [Na]. This section addresses the modeling of the effect on [Na] from change in [Glu] not accompanied by changes in external balance of body water or monovalent cations, i. Applying this principle and considering that the amounts of sodium in the extracellular compartment and effective solute in the intracellular compartment remain constant during development of hyperglycemia, Katz calculated that [Na] changes by 1. Goldberg proposed using the Katz coefficient to predict the value of [Na] after correction of hyperglycemia Subsequently, Al-Kudsi et al. provided the following formula to calculate this corrected [Na] 16 :. The Al-Kudsi formula predicts the value of [Na] after correction of [Glu] to 5. The corrected [Na] at any desired final value of [Glu] can be calculated by substituting this desired [Glu] for 5. The Katz report created new insights into the change in tonicity produced by glucose gain. As a matter of fact, the increase in total body effective solute baseline solute plus glucose gain causes equal rises in both intracellular and extracellular fluid tonicities. The glucose-induced gain in extracellular solute causes water exit from the cells 19 to bring about hypertonic hyponatremia Katz's coefficient computes tonicity increase ΔTon of 2. Several guidelines for managing hyperglycemia 21 — 24 and other reports 25 — 29 have adopted the Katz coefficient for calculating the corrected [Na]. Alternate guidelines for treating hyperglycemia 30 , 31 and hyponatremia 32 , and various other reports 33 — 35 advocate other coefficients. The variation of these coefficients resulted from both theoretical calculations and clinical studies. This section addresses the theoretical calculations. Note: In the text and Table 1 , the subscripts 1 and 2 denote respectively baseline euglycemia and hyperglycemia. Table 1. Tonicity-related and body fluid variables in a closed system of hyperglycemia. Total glucose gain during development of hyperglycemia is the product of ECFV 1 and [Glu] A. Table 1 shows general formulas used by Katz for computation of tonicity-related and volume-related parameters. Total intracellular and extracellular solutes in this Table are the total solutes determining tonicity Solutes with body water distribution, e. For all examples the baseline values were 5. For the same volume ratio α 1 , the same degree of hyperglycemia results in the same hypertonicity values regardless of the size of extracellular volume. ECFV 1 values are 16 and 32 L and glucose loads are 1, 16 × and 3, 32 × mmol, respectively. For comparable degrees of hyperglycemia, hypertonicity is higher in hypervolemia and lower in hypovolemia compared to euvolemia. Euvolemic values are shown in the previous example. b Differences in sodium concentration between plasma and interstitial compartment due to Gibbs-Donnan equilibrium between these two sub-compartments of the ECFV 17 ; c Exit of potassium from cells and changes in intracellular solute during development of hyperglycemia Finally, both definition and methods of measurement of ECFV encounter difficulties 43 , The difference between these corrected [Na] values has minimal clinical significance. Hyperglycemia in patients with advanced renal failure allows study of the theoretical predictions in a closed system because it can be treated with insulin infusion and with no or minimal changes in the external balance of sodium, potassium and water 45 , Mean ± standard deviation values at presentation and end of observation, respectively, were as follows: [Glu] Another study analyzed the relationship between [Glu] and [Na] by linear regression in patients on dialysis who had at least three measurements of [Glu] and [Na] and a difference between the lowest and highest value of [Glu] exceeding Hyperglycemic episodes in patients with preserved renal function represent a different entity. The next section addresses these patients. Severe hyperglycemia in patients with preserved renal function causes deficits in body sodium, potassium, and water, which are the key determinants of [Na] at euglycemia Balance abnormalities specific to hyperglycemia develop from water gain in the gastrointestinal tract and losses of water, sodium and potassium from the urinary tract. Thirst is caused by hyperglycemic hypertonicity and hypovolemia from urinary losses. Hyperglycemic hypertonicity caused thirst in animal experiments Polydipsia is a prominent clinical manifestation of hyperglycemic crises 7 , 52 , Water intake from hyperglycemia led to hyponatremia after correction with insulin of approximately one-third of the hyperglycemic episodes in dialysis patients A major rise in tonicity in hyperglycemia results from osmotic diuresis, in which water loss is relatively greater than loss of sodium plus potassium 5 , 17 , Thus, in hyperglycemic crises occurring in patients with preserved renal function, who represent an open system, [Na] receives influences from three pathophysiologic processes: rise in [Glu] and water gain cause [Na] decreases, while osmotic diuresis causes [Na] increase. In these patients, quantitating the isolated effect of glucose gain is imperative because this effect is predictable with a reasonable degree of certainty, as shown in the previous section, and more importantly, it will disappear with correction of hyperglycemia without requiring additional measures. Prediction of the quantitative effects of water intake and particularly of osmotic diuresis, which is the dominant effect on tonicity in severe hyperglycemic episodes 2 , 3 , is difficult because the magnitude of these processes varies greatly 2 , The effects of osmotic diuresis on [Na] require correction by fluid infusion. One report calculated the effects of osmotic diuresis on tonicity-related values in a hypothetical subject with extreme hyperglycemia [Glu] of This finding suggests that the corrected [Na] by the Al-Kudsi formula provides a reasonable prediction of the part of hypertonicity that is due to osmotic diuresis. Accounting for changes in external balances of water, sodium, and potassium during development and treatment of hyperglycemia is necessary for any evaluation of the corrected [Na] in patients with renal function. There is a paucity of studies in this area. These findings were used in the development of several guidelines 30 — Assuming baseline values of 5. According to these calculations, tonicity, after rising appropriately with [Glu] rising from 5. The guidelines for hyperglycemic crises address diabetic ketoacidosis DKA and hyperosmolar hyperglycemic state HHS 1 , 21 — The diagnostic features of DKA include low arterial blood pH and serum bicarbonate, presence of ketone bodies in serum and urine, a wide serum anion gap, and variable tonicity 1. However, euglycemic DKA has become more frequent after the introduction of sodium glucose cotransporter 2 SGLT-2 inhibitors in the treatment of diabetes mellitus Hypertonicity may cause coma in hyperglycemic syndromes 60 , At equal levels of hyperglycemic hypertonicity, elevated [Na] indicates severe water deficit 64 , The corrected [Na] illustrates the difference in water deficit between high [Na] and high [Glu] in this case. Table 2 shows presenting values for [Glu], [Na], tonicity, and corrected [Na] in reports of DKA 66 — , HHS 3 , 9 , 13 , 75 — 78 , , , , — , and hyperglycemia in chronic kidney disease CKD stage V 12 , 16 , 47 — 49 , , , — , which was included in Table 2 as the control group because it causes limited or no water and electrolyte losses through osmotic diuresis. All but three of the cases in this last group were on maintenance dialysis. To show the range of the tonicity-related values, Table 2 includes studies as well as case reports. Reports of combined DKA and HHS were included in the DKA part of the table. Studies reporting median, instead of mean, tonicity-related values were not included in this table. The reason for including these cases was explained above. Table 2. Presenting serum glucose, sodium, tonicity, and corrected sodium levels in reported hyperglycemic crises. In Table 2 , there exists considerable overlap of [Glu], [Na] tonicity, and corrected [Na] ranges in the three categories of hyperglycemia. DKA combined with HHS occurred in many instances. The term Diabetic Hyperosmolar Ketoacidosis DHKA was proposed for DKA combined with HHS Patients on dialysis who presented with hyperglycemia and elevated corrected [Na] have usually lost hypotonic fluids through hemodialysis , or peritoneal dialysis — , , with high glucose concentration in the dialysate. The second important finding in Table 2 is in the mean corrected [Na] values. Thus, although many patients have water deficits in excess of sodium and potassium deficits, an equal or even larger number of patients do not have excessive water deficits at presentation with DKA. This finding has important consequences in the choice of the tonicity of replacement solutions. Mean corrected [Na] was in the eunatremic range in hyperglycemia of patients with CKD stage 5. Preventing cerebral edema is a key concern during treatment of hyperglycemic crises. Tonicity-related parameters have received attention in the studies of the pathogenesis of this complication. These values do not differ substantially from the mean values of all DKA cases in Table 2. However, factors related to tonicity statistically associated with brain edema during treatment of DKA include decrease in tonicity, large early infusion volumes, very high [Glu] at presentation, rapid decline in [Glu], very low [Na], and administration of large doses of insulin , , The change in corrected [Na] during treatment of DKA was the best discriminator for the development of severe coma in one study Deterioration of neurological manifestations associated with substantial rises of the corrected [Na] has been reported during treatment of both DKA 2 , and HHS , , Other reported factors associated with cerebral edema in DKA include the degree of acidosis 96 , , , , high levels of blood urea at presentation , , and vasogenic factors One study found no effect of the rate of replacement fluid infusion The PECARN study found no significant differences in neurological manifestations during and following treatment of DKA between using 0. Vascular endothelial changes caused by elevated blood levels of cytokines and chemokines secondary to inflammatory status associated with DKA were proposed by the authors of the PECARN study as the main mechanism for the development of cerebral edema. High value of corrected [Na] at presentation with DKA is associated with increased incidence and severity of acute kidney injury AKI , Weighed mean values at presentation with DKA and AKI were AKI occurs frequently in HHS 3 , , , , , , Attention to tonicity plays a role in prevention of severe neurological manifestations during treatment of hyperglycemic emergencies. Decrease in tonicity from extracellular solute loss leads to osmotic entry of fluid into cells and could contribute to the development of cerebral edema For this reason, one report proposed a very slow decrease in tonicity during the early stages of treatment The optimal rate of decline in tonicity, however, has not been clarified. The change in tonicity due exclusively to correction of hyperglycemia has two components, a fall in [Glu] and a rise in [Na]. Guidelines propose hourly rates of 2. The corrected [Na] predicts the relation between effective body solute and total body water after decrease of [Glu] to its desired level 2 , 17 and should be used as a guide for the composition of replacement solutions in the same fashion as actual [Na] values are used to guide fluid management of dysnatremias 7 , — Evidence presented earlier supports the use of the Al-Kudsi formula for calculation of the corrected [Na]. Two limitations of the corrected [Na] should be addressed during treatment: First, the corrected [Na] using the Al-Kudsi formula is not accurate in some conditions, mainly in advanced extracellular volume disturbances. Second, and more importantly, the corrected [Na] reflects the relation between effective body solute and body water at the moment of blood sampling 2 , 17 , Correction of the extracellular volume deficit improves renal function and in the face of persistent hyperglycemia leads to large volume osmotic diuresis, which causes further water deficit and rises in the corrected [Na] 2. We propose the following scheme for use of the corrected [Na] during treatment of hyperglycemic crises: The initial measurement of serum values should include osmolality in addition to basic metabolic panel. In the absence of an exogenous solute e. In the second case, falsely low [Na] values are reported when this measurement is performed in an autoanalyzer that requires dilution of the samples measured If there is a large osmol gap, [Na] should be measured again in an apparatus that does not require dilution of the measured specimen, e. The tonicity of replacement solutions should be based on repeated calculations of the corrected [Na]. If the corrected [Na] at presentation is in the eunatremic range, infusion of isotonic saline should be started at a rate dictated by clinical manifestations of hypovolemia. Prevention of either decline or rise in the corrected [Na] is critical. Patients with corrected [Na] values within the normal range of [Na], like the average patient with DKA Table 2 , do not have relatively larger deficit of water compared to monovalent cations. In these patients, use of isotonic solutions as initial treatment of DKA and slow decline of [Glu], as proposed in the guidelines 1 , leads to rapid correction of severe extracellular volume deficits and prevents sharp changes in the corrected [Na]. In subjects with initial corrected [Na] in the eunatremic range, tonicity should decline at a low rate. Maintenance of the corrected [Na] at the same level and decrease in [Glu] at the rate proposed in the guidelines 2. In the rare instance of low presenting corrected [Na], or for treatment of cerebral edema, hypertonic saline infusion may be used During treatment, urine volume should be monitored and [Glu], [Na], serum potassium concentration, and other relevant parameters should be measured frequently, initially every 1—2 h. The corrected [Na] should be calculated after each measurement of [Glu] and [Na] and should guide changes in the tonicity of the infusate. Development of large osmotic diuresis may lead to increases in the corrected [Na] and the need for hypotonic infusions later in the course of treatment. A corrected [Na] in the hypernatremic range at presentation with hyperglycemia indicates excessive water deficit that must be corrected. Initially, infusion of isotonic fluids will correct rapidly volume deficits and will also decrease the level of hypertonicity. However, the subsequent development of large volume osmotic diuresis may lead to rise in the corrected [Na]. Monitoring urine volume, frequent measurement of the relevant serum biochemical values, and repeated calculation of the corrected [Na] after each measurement of [Glu] and [Na] is imperative. The corrected [Na] should not rise further; however, deciding whether it should remain at the same level at least early during the decrease in [Glu] or it should decrease at a slow rate e. Infusion of hypotonic solutions will eventually be needed regardless of whether the early phase of treatment aims at maintaining or decreasing the corrected [Na]. Addition of potassium salts to the infused saline should be guided by repeated measurements of the serum potassium concentration. In deciding the concentration of sodium in the replacement solutions, it is important to take into account the concentration of potassium salts in the infusate 2. The corrected [Na] calculated by the Al-Kudsi formula should guide the tonicity of replacement solutions. This use should be tempered by the knowledge that rarely encountered extreme volume disturbances can cause [Na] changes substantially different from those predicted by the corrected [Na] and, more importantly, that the corrected [Na] can vary greatly during treatment depending on changes in the external balances of water, sodium and potassium. For these reasons, frequent measurements of [Glu] and [Na], repeated calculation of the corrected [Na] after each measurement, and changes in the tonicity of replacement solutions based on the corrected [Na] are critical steps in the management of tonicity issues in hyperglycemia. Publicly available datasets were analyzed in this study. This data came from tables of publications cited in the text. TI: conceptualization. TI, KG, GB, CA, and AT: literature review. TI, GB, SL, and AT: methodology. SL, CA, and AT: visualization. TI and AT: writing-original draft preparation. KG, GB, SL, EA, and CA: writing-review and editing. All authors contributed to the article and approved the submitted version. GB was supported by a Burrows Wellcome Fund Career Award for Medical Scientists and NIH grant RO1 DK The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DM declared a past co-authorship with several of the authors TI, AT, and CA to the handling editor. The authors acknowledge Dialysis Clinic Inc. for supporting this work by covering publication expenses [DCI C]. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. doi: PubMed Abstract CrossRef Full Text Google Scholar. Tzamaloukas AH, Sun Y, Konstantinov NK, Ing TS, Dorin RI, Malhotra D, et al. 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Tzamaloukas AH, Khitan Z, Glew RH, Roumelioti M-A, Rondon-Berrios H, Elisaf MS, et al. Serum sodium concentration and tonicity in hyperglycemic crises: major influences and treatment implications. J Am Heart Assoc. Welt LG. Clinical Disorders of Hydration and Acid-Base Balance. Boston, MA: Little, Brown and Company Google Scholar. Seldin DW, Tarail R. Effect of hypertonic solutions on metabolism and excretion of electrolytes. Am J Physiol. Rondon-Berrios H, Agaba EI, Tzamaloukas AH. Hyponatremia: pathophysiology, classification, manifestations and management. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al. Management of hyperglycemic crises in patients with diabetes. Chiasson JL, Aris-Jilwan N, Bélanger R, Bertrand S, Beauregard H, Ekoé JM, et al. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Diabetes Canada Clinical Practice Guidelines Expert Committee, Goguen J, Gilbert J. Hyperglycemic emergencies in adults. Can J Diabetes. Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical Practice Consensus Guidelines Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. Harris GD, Fiordalisi I, Harris WL, Mosovich LL, Fibeg L. Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr. Harris GD, Fiordalisi I. Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in episodes. Arch Pediatr Adolesc Med. Oster JR, Singer I. Hyponatremia, hyposmolality, and hypotonicity: tables and fables. Arch Intern Med. Milionis HJ, Liamis G, Elisaf MS. Appropriate treatment of hypernatraemia in diabetic hyperglycaemic hyperosmolar syndrome. J Intern Med. Al-Mawed S, Pankratz VS, Chong K, Sandoval M, Roumelioti ME, Unruh M. Low serum sodium levels at hospital admission: outcomes among 2. PLoS ONE. Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Scott A on behalf of the Joint British Diabetes Societies JBDS for Inpatient Care. Management of hyperosmolar hyperglycaemic state in adults with diabetes. Diabet Med. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Hyponatremia Guideline Development Group. Clinical practice guidelines on diagnosis and treatment of hyponatraemia. Eur J Clin Endocrinol. Liamis G, Liberopoulos E, Barkas F, Elisaf M. Diabetes mellitus and electrolyte disorders. World J Clin Cases. Mohan S, Gu S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. Pipeleers L, Wissing KM, Hilbrands R. Acid-base and electrolyte disturbances in patients with diabetes mellitus. Acta Clin Belg. Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in patients with diabetes mellitus. Roscoe JM, Halperin ML, Rolleston FS, Goldstein MB. Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of the serum sodium depression. Can Med Assoc J. Robin AP, Ing TS, Lancaster GA, Soung LS, Sparagana M, Geis WP, et al. Hyperglycemia-induced hyponatremia: a fresh look. Clin Chem. Moran SM, Jamison RL. The variable hyponatremic response to hyperglycemia. West J Med. Tzamaloukas AH, Kyner WT, Galley WR Jr. Determinants of osmotic phenomena created by an isolated change in extracellular solute in anuria. Min Electrolyte Metab. Darrow DC, Yannett H. The change in the distribution of body water accompanying increase and decrease in extracellular electrolyte. J Clin Invest. Sterns RH. Disorders of plasma sodium- causes, consequences and correction. Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol. Roumelioti ME, Glew RH, Khitan ZJ, Rondon-Berrios H, Argyropoulos CP, Malhotra D, et al. Fluid balance concepts in medicine: principles and practice. Tzamaloukas AH, Ing TS, Siamopoulos KC, Raj DS, Elisaf MS, Rohrscheib M, et al. Pathophysiology and management of fluid and electrolyte disturbances in patients on chronic dialysis with severe hyperglycemia. Semin Dial. Sun Y, Roumelioti ME, Ganta K, Glew RH, Gibb J, Vigil D, et al. Dialysis-associated hyperglycemia: manifestations and treatment. Tzamaloukas AH, Rohrscheib M, Ing TS, Siamopoulos KC, Elisaf MF, Spalding CT. Serum tonicity, extracellular volume and clinical manifestations in symptomatic dialysis-associated hyperglycemia treated only with insulin. Int J Artif Organs. Tzamaloukas AH, Ing TS, Siamopoulos KC, Rohrscheib M, Elisaf MS, Raj DSC, et al. Body fluid abnormalities in severe hyperglycemia in patients on chronic dialysis: review of published reports. J Diabetes Complications. Penne EL, Thijssen S, Raimann JG, Levin NW, Kotanko P. Correction of serum sodium for glucose concentration in hemodialysis patients with poor glucose control. Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. Fitzsimons JT. The physiological basis of thirst. Kidney Int. Nyenwe EA, Kitabchi AE. The evolution of diabetic ketoacidosis: an update of its etiology, pathogenesis and management. Fayfman M, Pasquel FJ, Umpierrez GE. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Gennari FJ, Kassirer JP. Osmotic diuresis. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Shalwitz RA, Gingerich RL, McGill JB, McDonald JM. Effect of hyperglycemia in plasma sodium and potassium concentration revisited. Yu X, Zhang S, Zhang L. Newer perspectives of mechanisms for euglycemic diabetic ketoacidosis. Int J Endocrinol. The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to the release of free fatty acids into the circulation from adipose tissue lipolysis and to unrestrained hepatic fatty acid oxidation in the liver to ketone bodies β-hydroxybutyrate and acetoacetate 19 , with resulting ketonemia and metabolic acidosis. Increasing evidence indicates that the hyperglycemia in patients with hyperglycemic crises is associated with a severe inflammatory state characterized by an elevation of proinflammatory cytokines tumor necrosis factor-α and interleukin-β, -6, and -8 , C-reactive protein, reactive oxygen species, and lipid peroxidation, as well as cardiovascular risk factors, plasminogen activator inhibitor-1 and free fatty acids in the absence of obvious infection or cardiovascular pathology All of these parameters return to near-normal values with insulin therapy and hydration within 24 h. The procoagulant and inflammatory states may be due to nonspecific phenomena of stress and may partially explain the association of hyperglycemic crises with a hypercoagulable state The pathogenesis of HHS is not as well understood as that of DKA, but a greater degree of dehydration due to osmotic diuresis and differences in insulin availability distinguish it from DKA 4 , Although relative insulin deficiency is clearly present in HHS, endogenous insulin secretion reflected by C-peptide levels appears to be greater than in DKA, where it is negligible Table 2. Insulin levels in HHS are inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent lipolysis and subsequent ketogenesis IRI, immunoreactive insulin. Adapted from ref. The most common precipitating factor in the development of DKA and HHS is infection 1 , 4 , Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and drugs 10 , 13 , In addition, new-onset type 1 diabetes or discontinuation of insulin in established type 1 diabetes commonly leads to the development of DKA. Factors that may lead to insulin omission in younger patients include fear of weight gain with improved metabolic control, fear of hypoglycemia, rebellion against authority, and stress of chronic disease. Before , the use of continuous subcutaneous insulin infusion devices had also been associated with an increased frequency of DKA 23 ; however, with improvement in technology and better education of patients, the incidence of DKA appears to have reduced in pump users. However, additional prospective studies are needed to document reduction of DKA incidence with the use of continuous subcutaneous insulin infusion devices Underlying medical illness that provokes the release of counterregulatory hormones or compromises the access to water is likely to result in severe dehydration and HHS. In most patients with HHS, restricted water intake is due to the patient being bedridden and is exacerbated by the altered thirst response of the elderly. Elderly individuals with new-onset diabetes particularly residents of chronic care facilities or individuals with known diabetes who become hyperglycemic and are unaware of it or are unable to take fluids when necessary are at risk for HHS 10 , Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, and pentamidine, may precipitate the development of HHS or DKA 4. Recently, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs may cause hyperglycemia and even DKA or HHS 26 , An increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes. Observational and prospective studies indicate that over half of newly diagnosed adult African American and Hispanic subjects with unprovoked DKA have type 2 diabetes 28 , , , — The clinical presentation in such cases is acute as in classical type 1 diabetes ; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents. In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of β-cell destruction, and the ability to discontinue insulin therapy during follow-up 28 , 31 , This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes. At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA 28 , 31 , The process of HHS usually evolves over several days to weeks, whereas the evolution of the acute DKA episode in type 1 diabetes or even in type 2 diabetes tends to be much shorter. Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present with DKA with no prior clues or symptoms. For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, weight loss, vomiting, dehydration, weakness, and mental status change. Physical findings may include poor skin turgor, Kussmaul respirations in DKA , tachycardia, and hypotension. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS. Focal neurologic signs hemianopia and hemiparesis and seizures focal or generalized may also be features of HHS 4 , Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation. Severe hypothermia, if present, is a poor prognostic sign Caution needs to be taken with patients who complain of abdominal pain on presentation because the symptoms could be either a result of the DKA or an indication of a precipitating cause of DKA, particularly in younger patients or in the absence of severe metabolic acidosis 34 , Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis. The diagnostic criteria for DKA and HHS are shown in Table 1. The initial laboratory evaluation of patients include determination of plasma glucose, blood urea nitrogen, creatinine, electrolytes with calculated anion gap , osmolality, serum and urinary ketones, and urinalysis, as well as initial arterial blood gases and a complete blood count with a differential. An electrocardiogram, chest X-ray, and urine, sputum, or blood cultures should also be obtained. The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis blood pH, bicarbonate, and ketones and the presence of altered mental status 4. Significant overlap between DKA and HHS has been reported in more than one-third of patients Severe hyperglycemia and dehydration with altered mental status in the absence of significant acidosis characterize HHS, which clinically presents with less ketosis and greater hyperglycemia than DKA. This may result from a plasma insulin concentration as determined by baseline and stimulated C-peptide [ Table 2 ] adequate to prevent excessive lipolysis and subsequent ketogenesis but not hyperglycemia 4. The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration. Assessment of augmented ketonemia is usually performed by the nitroprusside reaction, which provides a semiquantitative estimation of acetoacetate and acetone levels. Although the nitroprusside test both in urine and in serum is highly sensitive, it can underestimate the severity of ketoacidosis because this assay does not recognize the presence of β-hydroxybutyrate, the main metabolic product in ketoacidosis 4 , If available, measurement of serum β-hydroxybutyrate may be useful for diagnosis Accumulation of ketoacids results in an increased anion gap metabolic acidosis. Hyperglycemia is a key diagnostic criterion of DKA; however, a wide range of plasma glucose can be present on admission. Elegant studies on hepatic glucose production rates have reported rates ranging from normal or near normal 38 to elevated 12 , 15 , possibly contributing to the wide range of plasma glucose levels in DKA that are independent of the severity of ketoacidosis This could be due to a combination of factors, including exogenous insulin injection en route to the hospital, antecedent food restriction 39 , 40 , and inhibition of gluconeogenesis. On admission, leukocytosis with cell counts in the 10,—15, mm 3 range is the rule in DKA and may not be indicative of an infectious process. In ketoacidosis, leukocytosis is attributed to stress and maybe correlated to elevated levels of cortisol and norepinephrine The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia. An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss. To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1. Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation 9 , Serum potassium concentration may be elevated because of an extracellular shift of potassium caused by insulin deficiency, hypertonicity, and acidemia Patients with low normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia. Pseudonormoglycemia 44 and pseudohyponatremia 45 may occur in DKA in the presence of severe chylomicronemia. The admission serum phosphate level in patients with DKA, like serum potassium, is usually elevated and does not reflect an actual body deficit that uniformly exists due to shifts of intracellular phosphate to the extracellular space 12 , 46 , Insulin deficiency, hypertonicity, and increased catabolism all contribute to the movement of phosphate out of cells. A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis; however, lipase could also be elevated in DKA in the absence of pancreatitis Not all patients with ketoacidosis have DKA. DKA must also be distinguished from other causes of high—anion gap metabolic acidosis, including lactic acidosis; ingestion of drugs such as salicylate, methanol, ethylene glycol, and paraldehyde; and acute chronic renal failure 4. Because lactic acidosis is more common in patients with diabetes than in nondiabetic persons and because elevated lactic acid levels may occur in severely volume-contracted patients, plasma lactate should be measured on admission. A clinical history of previous drug abuse should be sought. Measurement of serum salicylate and blood methanol level may be helpful. Ethylene glycol antifreeze is suggested by the presence of calcium oxalate and hippurate crystals in the urine. Paraldehyde ingestion is indicated by its characteristic strong odor on the breath. Because these intoxicants are low—molecular weight organic compounds, they can produce an osmolar gap in addition to the anion gap acidosis A recent report states that active cocaine use is an independent risk factor for recurrent DKA Recently, one case report has shown that a patient with diagnosed acromegaly may present with DKA as the primary manifestation of the disease In addition, an earlier report of pituitary gigantism was presented with two episodes of DKA with complete resolution of diabetes after pituitary apoplexy Successful treatment of DKA and HHS requires correction of dehydration, hyperglycemia, and electrolyte imbalances; identification of comorbid precipitating events; and above all, frequent patient monitoring. Protocols for the management of patients with DKA and HHS are summarized in Fig. Protocol for management of adult patients with DKA or HHS. Bwt, body weight; IV, intravenous; SC, subcutaneous. Initial fluid therapy is directed toward expansion of the intravascular, interstitial, and intracellular volume, all of which are reduced in hyperglycemic crises 53 and restoration of renal perfusion. In the absence of cardiac compromise, isotonic saline 0. Subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urinary output. In general, 0. Fluid replacement should correct estimated deficits within the first 24 h. In patients with renal or cardiac compromise, monitoring of serum osmolality and frequent assessment of cardiac, renal, and mental status must be performed during fluid resuscitation to avoid iatrogenic fluid overload 4 , 10 , 15 , Aggressive rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy During treatment of DKA, hyperglycemia is corrected faster than ketoacidosis. The mainstay in the treatment of DKA involves the administration of regular insulin via continuous intravenous infusion or by frequent subcutaneous or intramuscular injections 4 , 56 , Randomized controlled studies in patients with DKA have shown that insulin therapy is effective regardless of the route of administration The administration of continuous intravenous infusion of regular insulin is the preferred route because of its short half-life and easy titration and the delayed onset of action and prolonged half-life of subcutaneous regular insulin 36 , 47 , Numerous prospective randomized studies have demonstrated that use of low-dose regular insulin by intravenous infusion is sufficient for successful recovery of patients with DKA. Until recently, treatment algorithms recommended the administration of an initial intravenous dose of regular insulin 0. A recent prospective randomized study reported that a bolus dose of insulin is not necessary if patients receive an hourly insulin infusion of 0. Phosphate concentration decreases with insulin therapy. Prospective randomized studies have failed to show any beneficial effect of phosphate replacement on the clinical outcome in DKA 32 , and overzealous phosphate therapy can cause severe hypocalcemia with no evidence of tetany 17 , No studies are available on the use of phosphate in the treatment of HHS. Continuous monitoring using a flowsheet Fig. Commonly, patients recovering from DKA develop hyperchloremia caused by the use of excessive saline for fluid and electrolyte replacement and transient non-anion gap metabolic acidosis as chloride from intravenous fluids replaces ketoanions lost as sodium and potassium salts during osmotic diuresis. These biochemical abnormalities are transient and are not clinically significant except in cases of acute renal failure or extreme oliguria. Cerebral edema is a rare but frequently fatal complication of DKA, occurring in 0. It is most common in children with newly diagnosed diabetes, but it has been reported in children with known diabetes and in young people in their twenties 25 , Fatal cases of cerebral edema have also been reported with HHS. Clinically, cerebral edema is characterized by a deterioration in the level of consciousness, with lethargy, decrease in arousal, and headache. Neurological deterioration may be rapid, with seizures, incontinence, pupillary changes, bradycardia, and respiratory arrest. These symptoms progress as brain stem herniation occurs. The progression may be so rapid that papilledema is not found. Although the mechanism of cerebral edema is not known, it likely results from osmotically driven movement of water into the central nervous system when plasma osmolality declines too rapidly with the treatment of DKA or HHS. There is a lack of information on the morbidity associated with cerebral edema in adult patients; therefore, any recommendations for adult patients are clinical judgements, rather than scientific evidence. Hypoxemia and, rarely, noncardiogenic pulmonary edema may complicate the treatment of DKA. Hypoxemia is attributed to a reduction in colloid osmotic pressure that results in increased lung water content and decreased lung compliance. Patients with DKA who have a widened alveolo-arteriolar oxygen gradient noted on initial blood gas measurement or with pulmonary rales on physical examination appear to be at higher risk for the development of pulmonary edema. Many cases of DKA and HHS can be prevented by better access to medical care, proper education, and effective communication with a health care provider during an intercurrent illness. The observation that stopping insulin for economic reasons is a common precipitant of DKA in urban African-Americans 35 , 36 is disturbing and underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious. Sick-day management should be reviewed periodically with all patients. It should include specific information on 1 when to contact the health care provider, 2 blood glucose goals and the use of supplemental short-acting insulin during illness, 3 means to suppress fever and treat infection, and 4 initiation of an easily digestible liquid diet containing carbohydrates and salt. Most importantly, the patient should be advised to never discontinue insulin and to seek professional advice early in the course of the illness. Adequate supervision and help from staff or family may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition. Better education of care givers as well as patients regarding signs and symptoms of new-onset diabetes; conditions, procedures, and medications that worsen diabetes control; and the use of glucose monitoring could potentially decrease the incidence and severity of HHS. The annual incidence rate for DKA from population-based studies ranges from 4. Significant resources are spent on the cost of hospitalization. Many of these hospitalizations could be avoided by devoting adequate resources to apply the measures described above. Because repeated admissions for DKA are estimated to drain approximately one of every two health care dollars spent on adult patients with type 1 diabetes, resources need to be redirected toward prevention by funding better access to care and educational programs tailored to individual needs, including ethnic and personal health care beliefs. In addition, resources should be directed toward the education of primary care providers and school personnel so that they can identify signs and symptoms of uncontrolled diabetes and new-onset diabetes can be diagnosed at an earlier time. This has been shown to decrease the incidence of DKA at the onset of diabetes 30 , Protocol for the management of adult patients with DKA. Normal ranges vary by lab; check local lab normal ranges for all electrolytes. Obtain chest X-ray and cultures as needed. IM, intramuscular; IV, intravenous; SC subcutaneous. Protocol for the management of adult patients with HHS. This protocol is for patients admitted with mental status change or severe dehydration who require admission to an intensive care unit. For less severe cases, see text for management guidelines. IV, intravenous; SC subcutaneous. From Kitabchi et al. See text for details. Data are from Ennis et al. The highest ranking A is assigned when there is supportive evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered, including evidence from a meta-analysis that incorporated quality ratings in the analysis. An intermediate ranking B is given to supportive evidence from well-conducted cohort studies, registries, or case-control studies. A lower rank C is assigned to evidence from uncontrolled or poorly controlled studies or when there is conflicting evidence with the weight of the evidence supporting the recommendation. Expert consensus E is indicated, as appropriate. For a more detailed description of this grading system, refer to Diabetes Care 24 Suppl. The recommendations in this paper are based on the evidence reviewed in the following publication: Management of hyperglycemic crises in patients with diabetes Technical Review. Diabetes Care —, The initial draft of this position statement was prepared by Abbas E. Kitabchi, PhD, MD; Guillermo E. Umpierrez, MD; Mary Beth Murphy, RN, MS, CDE, MBA; Eugene J. Barrett, MD, PhD; Robert A. Kreisberg, MD; John I. Malone, MD; and Barry M. Wall, MD. The paper was peer-reviewed, modified, and approved by the Professional Practice Committee and the Executive Committee, October Revised Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Previous Article. Article Navigation. Position Statements January 01 Hyperglycemic Crises in Diabetes American Diabetes Association American Diabetes Association. This Site. Google Scholar. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1—. View large Download slide. Figure 2—. Figure 3—. Figure 4—. Table 1— Diagnostic criteria for DKA and HHS. View Large. Table 3— Summary of major recommendations. Therefore, to avoid the occurrence of cerebral edema, follow the recommendations in the position statement regarding a gradual correction of glucose and osmolality as well as the judicious use of isotonic or hypotonic saline, depending on serum sodium and the hemodynamic status of the patient.

Diabetes mellitus DM affects the metabolism of primary macronutrients such as proteins, fats, and carbohydrates. Due to the Workout apparel recommendations prevalence imbalancex DM, emergency admissions for hyperglycemic crisis, diabetic imbqlances DKA Electrolyhe hyperglycemic Diuretic effect of caffeine state HHS are fairly common and represent very challenging clinical management in practice. DKA and HHS are associated with high mortality rates if left not treated. DKA and HHS have similar pathophysiology with some few differences. HHS pathophysiology is not fully understood. However, an absolute or relative effective insulin concentration reduction and increased in catecholamines, cortisol, glucagon, and growth hormones represent the mainstay behind DKA pathophysiology.

Hyperglycemic crisis and electrolyte imbalances -
Sign In. Skip Nav Destination Close navigation menu Article navigation. Previous Article. Article Navigation. Position Statements January 01 Hyperglycemic Crises in Diabetes American Diabetes Association American Diabetes Association. This Site. Google Scholar. Get Permissions.

toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1—. View large Download slide. Figure 2—. Figure 3—. Figure 4—. Table 1— Diagnostic criteria for DKA and HHS. View Large. Table 3— Summary of major recommendations.

Therefore, to avoid the occurrence of cerebral edema, follow the recommendations in the position statement regarding a gradual correction of glucose and osmolality as well as the judicious use of isotonic or hypotonic saline, depending on serum sodium and the hemodynamic status of the patient.

McGarry JD, Woeltje KF, Kuwajima M, Foster DW: Regulation of ketogenesis and the renaissance of carnitine palmitoyl transferase. Diabetes Metab Rev. DeFronzo RA, Matsuda M, Barrett E: Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy.

Diabetes Rev. Atchley DW, Loeb RF, Richards DW, Benedict EM, Driscoll ME: A detailed study of electrolyte balances following withdrawal and reestablishment of insulin therapy. J Clin Invest.

Halperin ML, Cheema-Dhadli S: Renal and hepatic aspects of ketoacidosis: a quantitative analysis based on energy turnover. Malone ML, Gennis V, Goodwin JS: Characteristics of diabetic ketoacidosis in older versus younger adults.

J Am Geriatr Soc. Matz R: Hyperosmolar nonacidotic diabetes HNAD. In Diabetes Mellitus: Theory and Practice. Morris LE, Kitabchi AE: Coma in the diabetic.

In Diabetes Mellitus: Problems in Management. Kreisberg RA: Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment. Ann Int Med. Klekamp J, Churchwell KB: Diabetic ketoacidosis in children: initial clinical assessment and treatment.

Pediatric Annals. Glaser NS, Kupperman N, Yee CK, Schwartz DL, Styne DM: Variation in the management of pediatric diabetic ketoacidosis by specialty training.

Arch Pediatr Adolescent Med. Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM: Management of hyperglycemic crises in patients with diabetes mellitus Technical Review. Diabetes Care.

Beigelman PM: Severe diabetic ketoacidosis diabetic coma : episodes in patients: experience of three years. Polonsky WH, Anderson BJ, Lohrer PA, Aponte JE, Jacobson AM, Cole CF: Insulin omission in women with IDDM. Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ: Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state.

Ennis ED, Stahl EJVB, Kreisberg RA: The hyperosmolar hyperglycemic syndrome. Marshall SM, Walker M, Alberti KGMM: Diabetic ketoacidosis and hyperglycaemic non-ketotic coma. In International Textbook of Diabetes Mellitus. Carroll P, Matz R: Uncontrolled diabetes mellitus in adults: experience in treating diabetic ketoacidosis and hyperosmolar coma with low-dose insulin and uniform treatment regimen.

Ennis ED, Stahl EJ, Kreisberg RA: Diabetic ketoacidosis. Hillman K: Fluid resuscitation in diabetic emergencies: a reappraisal. Intensive Care Med. Fein IA, Rackow EC, Sprung CL, Grodman R: Relation of colloid osmotic pressure to arterial hypoxemia and cerebral edema during crystalloid volume loading of patients with diabetic ketoacidosis.

Ann Intern Med. Matz R: Hypothermia in diabetic acidosis. Kitabchi AE, Sacks HS, Young RT, Morris L: Diabetic ketoacidosis: reappraisal of therapeutic approach.

Ann Rev Med. Mahoney CP, Vleck BW, DelAguila M: Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurology. Finberg L: Why do patients with diabetic ketoacidosis have cerebral swelling, and why does treatment sometimes make it worse?

Pediatr Adolescent Med. Duck SC, Wyatt DT: Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr. Kitabchi AE, Ayyagari V, Guerra SMO, Medical House Staff: The efficacy of low dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis.

Fisher JN, Shahshahani MN, Kitabchi AE: Diabetic ketoacidosis: low dose insulin therapy by various routes. N Engl J Med. Barnes HV, Cohen RD, Kitabchi AE, Murphy MB: When is bicarbonate appropriate in treating metabolic acidosis including diabetic ketoacidosis?

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Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, Bertrand JC: Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med. Fisher JN, Kitabchi AE: A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab.

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Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Umpierrez GE, Kelly JP, Navarrete JE, Casals MMC, Kitabchi AE: Hyperglycemic crises in urban blacks.

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Pediatr Annals. Frequent blood glucose monitoring every 1—2 h is mandatory to recognize hypoglycemia because many patients with DKA who develop hypoglycemia during treatment do not experience adrenergic manifestations of sweating, nervousness, fatigue, hunger, and tachycardia.

Hyperchloremic non—anion gap acidosis, which is seen during the recovery phase of DKA, is self-limited with few clinical consequences This may be caused by loss of ketoanions, which are metabolized to bicarbonate during the evolution of DKA and excess fluid infusion of chloride containing fluids during treatment 4.

Symptoms and signs of cerebral edema are variable and include onset of headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary changes, papilledema, bradycardia, elevation in blood pressure, and respiratory arrest Manitol infusion and mechanical ventilation are suggested for treatment of cerebral edema Many cases of DKA and HHS can be prevented by better access to medical care, proper patient education, and effective communication with a health care provider during an intercurrent illness.

Paramount in this effort is improved education regarding sick day management, which includes the following:. Emphasizing the importance of insulin during an illness and the reasons never to discontinue without contacting the health care team.

Similarly, adequate supervision and staff education in long-term facilities may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition. The use of home glucose-ketone meters may allow early recognition of impending ketoacidosis, which may help to guide insulin therapy at home and, possibly, may prevent hospitalization for DKA.

In addition, home blood ketone monitoring, which measures β-hydroxybutyrate levels on a fingerstick blood specimen, is now commercially available The observation that stopping insulin for economic reasons is a common precipitant of DKA 74 , 75 underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious.

The rate of insulin discontinuation and a history of poor compliance accounts for more than half of DKA admissions in inner-city and minority populations 9 , 74 , Several cultural and socioeconomic barriers, such as low literacy rate, limited financial resources, and limited access to health care, in medically indigent patients may explain the lack of compliance and why DKA continues to occur in such high rates in inner-city patients.

These findings suggest that the current mode of providing patient education and health care has significant limitations. Addressing health problems in the African American and other minority communities requires explicit recognition of the fact that these populations are probably quite diverse in their behavioral responses to diabetes Significant resources are spent on the cost of hospitalization.

Based on an annual average of , hospitalizations for DKA in the U. A recent study 2 reported that the cost burden resulting from avoidable hospitalizations due to short-term uncontrolled diabetes including DKA is substantial 2.

However, the long-term impact of uncontrolled diabetes and its economic burden could be more significant because it can contribute to various complications. Because most cases occur in patients with known diabetes and with previous DKA, resources need to be redirected toward prevention by funding better access to care and educational programs tailored to individual needs, including ethnic and personal health care beliefs.

In addition, resources should be directed toward the education of primary care providers and school personnel so that they can identify signs and symptoms of uncontrolled diabetes and so that new-onset diabetes can be diagnosed at an earlier time.

Recent studies suggest that any type of education for nutrition has resulted in reduced hospitalization In fact, the guidelines for diabetes self-management education were developed by a recent task force to identify ten detailed standards for diabetes self-management education An American Diabetes Association consensus statement represents the authors' collective analysis, evaluation, and opinion at the time of publication and does not represent official association opinion.

Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 32, Issue 7.

Previous Article Next Article. Article Navigation. Consensus Statements July 01 Hyperglycemic Crises in Adult Patients With Diabetes Abbas E. Kitabchi, PHD, MD ; Abbas E. Kitabchi, PHD, MD. Corresponding author: Abbas E.

Kitabchi, akitabchi utmem. This Site. Google Scholar. Guillermo E. Umpierrez, MD ; Guillermo E. Umpierrez, MD. John M. Miles, MD ; John M. Miles, MD. Joseph N. Fisher, MD Joseph N. Fisher, MD. Diabetes Care ;32 7 — Get Permissions. toolbar search Search Dropdown Menu.

toolbar search search input Search input auto suggest. Table 1 Diagnostic criteria for DKA and HHS. Arterial pH 7. View Large. Figure 1. View large Download slide.

Pathogenesis of DKA and HHS: stress, infection, or insufficient insulin. FFA, free fatty acid. Table 2 Admission biochemical data in patients with HHS or DKA. Figure 2. Early contact with the health care provider. Review of blood glucose goals and the use of supplemental short- or rapid-acting insulin.

Having medications available to suppress a fever and treat an infection. Initiation of an easily digestible liquid diet containing carbohydrates and salt when nauseated. No potential conflicts of interest relevant to this article were reported.

National Center for Health Statistics. Burden of hospitalizations primarily due to uncontrolled diabetes: implications of inadequate primary health care in the United States. Search ADS. Agency for Healthcare Research and Quality. Databases and related tools from the healthcare cost and utilization project HCUP [article online].

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Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion. Sever hyperglycemic hyperosmolar nonketotic coma in a nondiabetic patient receiving aripiprazole.

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Internal Hyperrglycemic Rapid Refreshers is a series of concise information-packed videos refreshing your knowledge on Glutamine and muscle repair medical issues that Vrisis practitioners may encounter in their daily practice. Hyperblycemic episode reviews Hyperglyycemic key aspects of the management of imgalances ketoacidosis. Introduction Pathophysiology Hyperglycemmic presentation and e,ectrolyte Management Hyperglycemic crisis and electrolyte imbalances Hemodynamic instability Management: Electrolyte abnormalities Management: Anion gap metabolic acidosis Management: Hyperglycemia Management: Identification and treatment of the precipitating cause Management: Other Credits. Infographic courtesy of The Intern at Work theinternatwork. Chapter on diabetic ketoacidosis from the McMaster Textbook of Internal Medicine guidelines for the prevention and management of diabetes by Diabetes Canada Anion gap calculator at mdcalc. This Rapid Refresher video will describe a practical approach to diagnosis and management of diabetic ketoacidosis DKA. It is targeted to independently practicing subspecialists who are returning to general internal medicine and who want to brush up on their knowledge.

2 thoughts on “Hyperglycemic crisis and electrolyte imbalances”

Vudoshakar:

12.12.2023 в 15:12

Ich denke, dass Sie nicht recht sind. Schreiben Sie mir in PM, wir werden reden.

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Viramar:

13.12.2023 в 02:41

Ja, ich verstehe Sie. Darin ist etwas auch den Gedanken ausgezeichnet, ist mit Ihnen einverstanden.

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Hyperglycemic crisis and electrolyte imbalances

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